Project Summary/Abstract We propose to determine a how tick peritrophic membrane (PM) protein, named as putative chitin binding protein (CBP), influences PM formation as well as Borrelia burgdorferi infectivity in ticks. Lyme disease, a prevalent arthropod-borne disease in North America, is caused by spirochetal bacteria Borrelia burgdorferi, transmitted by Ixodes scapularis (I. scapularis) ticks. In nature, nave ticks acquire the spirochete via feeding on infected animals. Humans and many domesticated animals are accidental hosts of ticks. Once transmitted from infected ticks to hosts, B. burgdorferi can colonize a variety of target tissues causing a number of serious clinical complications. Despite there are more than 300,000 new estimated cases of Lyme disease in the United States every year and recent emergence of new and more virulent strains of B. burgdorferi sensu lato in the United States < http://www.cdc.gov/media/releases/2016/p0208-lyme-disease.html >, a vaccine to prevent human infection unavailable. The tick gut represents the microbial entry point and also serves as the major organ for pathogen colonization and survival within the vector. The PM, which is an acellular strip-like structure, is formed during early stages of blood meal engorgement in ticks, is primarily composed of chitin microfibrils embedded in a matrix of proteins, such as chitin-binding proteins and glycoproteins. It covers the whole surface of the gut, physically separating the gut lumen from the epithelium [10]. Acting as an effective mechanical barrier, the PM prevents damage to gut cells from by ingested products and toxins and keeps the stability of the gut environment. In many arthropods, such as mosquitoes, a permanent PM structure exists before the intake of a blood meal. Notably, in ticks, the PM is transiently formed during the early course of feeding, which provides an opportunity to interfere with PM structure using inhibitors or specific antibodies directed against PM components critical for its formation or function. Here, we characterized a potential tick PM protein, termed as CBP for its roles in PM formation as well as B. burgdorferi survival within the vector. The goal of the current proposal is to further characterize biological functions of CBP and its use as a novel tick vaccine against Lyme disease.